Treatment of disorders of the musculoskeletal system, such as skeletal deformities and traumatic injuries that result in fractures, frequently involve the use of orthopedic implants. Of key importance in this field is the assurance that orthopedic implants are permanently and securely set in place. Implant failure can result in additional surgical procedures, severe discomfort to the patient and delay of rehabilitation. Moreover, the overall cost of revision surgery frequently exceeds the cost of primary intervention and poses an additional risk to the patient.
The most common cause of orthopedic implant failure is a suboptimal bone-implant interface, caused by the lack of integration of the implant into the bone structure (osseointegration), frequently leading to aseptic loosening. The process of osseointegration involves the bone healing around and incorporating into the surface of the orthopedic device. Healing occurs as specialized cells, osteoblasts, secrete both the organic and inorganic components of the bone matrix, which is a gel-like substance that becomes mineralized during the healing process. It is this mineralization that sets the implant in place and provides integration of the material of the implant into the bone. Thus, the design of implants materials and coatings that promote mineralization and osseointegration is a high priority in the orthopedics field.
The main osseointegration coatings that are in clinical use today are metal oxide micron beads, hydroxyapatite crystal coatings, calcium phosphate composites (Ca—P), bioactive glass, and titanium (Ti) and titanium alloy films. Both the titanium alloy films and micron beads have been shown to adhere effectively to the bone and expedite osseointegration. Titanium alloy and hydroxyapatite crystal coatings have been shown to increase healing time significantly and are currently in use for dental implants, pins, screws, and femoral stems in hip replacements. Similarly, Ca—P has been used to coat titanium devices and is known to stimulate bone formation and to intensify bonding strength. Bioactive glasses composed of different proportions of SiO2, Na2O, CaO, and P2O4 are osteogenic and allow osteoblasts to migrate through the material.
Although all of these coatings may successfully be used clinically, they have inherent limitations including low volumetric porosity, high modulus of elasticity, low frictional characteristics compared to natural bone, and reduced longevity. For instance, the high temperature process needed to deposit titanium nitride on the surface of an implant can amplify cracks and increase the fatigue rate of the implant. Furthermore, the titanium nitride coatings have been shown to release metal ions over time and show wear defects after maintaining loads for a year. Both the bioactive hydroxyapatite crystals and Ca—P coatings tend to fail due to interfacial fracture or delamination between the implant and bone. Similarly, while silicate-based glasses can be used to coat titanium implants, apatite, a mineral component of bone, does not form well on such surfaces and the mechanical properties of glass do not allow the high loads frequently encountered by orthopedic implants. Consequently, the shortcomings of the current coatings underlie the need for new materials that can increase osseointegration of implants.
The method of production of nanostructures, especially silicon dioxide nanostructures, the binding of nanostructures onto a surface of a substrate material, the optional coating of nanostructures, and several uses of coated and uncoated nanostructures are disclosed in International Applications PCT/US2006/024435 and PCT/US2010/053880, U.S. Pat. No. 7,771,512, and U.S. Patent Application No. 2010/0215915, the disclosures of which are incorporated herein in their entirety. These patent documents disclose how the nanostructures are made and their use in fields such as for gas sensors, optical sensors, molecular sensors, hydrogen storage devices, catalytic converters, and for photocatalytic conversion of carbon dioxide.
Recently, several authors have disclosed the use of nanomaterials to increase bone cell proliferation and osteogenesis. Oh et al, Journal of Biomedical Materials Research Part A, DOI:10.1002/jbm.a (2006), discloses an increase in osteogenesis obtained with vertically aligned titanium dioxide nanotubes. Ruckh et al, Nanotechnology, 20 (2009) 045102 (7 pp), similarly discloses that an increase in osteogenesis is obtained with vertically aligned tantalum oxide nanotubes. None of these materials has been approved for use in veterinary or human medicine and problems persist with these nanostructural implants.
The prior art dealing with nanostructures and osseointegration concerns vertically aligned nanostructures, specifically nanotubes. Such structures provide a less than ideal substrate for osteogenesis because the aligned nanostructures do not form a nanostructure mat in which the nanomaterials are disordered and inter-related in a morphology similar to that which is formed by connective collagen networks found in healing bone. Thus, a need exists for a nanostructure that more closely mimics the structure of such collagen and that will be more suitable for the stimulation of osseointegration.